An improved low-permeability in vitro-model of the blood-brain barrier: transport studies on retinoids, sucrose, haloperidol, caffeine and mannitol

被引:125
作者
Franke, H [1 ]
Galla, HJ [1 ]
Beuckmann, CT [1 ]
机构
[1] Univ Munster, Inst Biochem, D-48149 Munster, Germany
关键词
cell culture; blood-brain barrier; porcine; transport; retinoid; sucrose;
D O I
10.1016/S0006-8993(98)01282-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Primary cultures of porcine brain capillary endothelial cells grown on collagen coated polycarbonate membranes were used to build up an in vitro-model for the blood-brain barrier. Improved cultivation techniques allowed cell-storage and experiments under serum-free conditions. We employed this model to perform permeability studies in vitro with the radioactively labelled marker substances sucrose, retinoic acid, retinol, haloperidol, caffeine, and mannitol. Permeability values obtained with this blood-brain barrier model (1.0 x 10(-6) cm/s for sucrose, 6.2 x 10(-6) cm/s for retinoic acid, 4.8 x 10(-6) cm/s for retinol, 49.5 x 10(-6) cm/s for haloperidol, 62.4 x 10(-6) cm/s for caffeine, and 1.8 x 10(-6) cm/s for mannitol) show a good correlation to data which are already known from in vivo-experiments. As judged by the sucrose permeability our blood-brain barrier model is less permeable than numerous other models published so far. Therefore it represents a powerful tool for in vitro-prediction of blood-brain barrier permeability of drugs and offers the possibility to scan a large quantity of drugs for their potential to enter the brain. (C) 1999 Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:65 / 71
页数:7
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